Biomedical subjects

S R Wisniewski

Publications and source records attributed to S R Wisniewski.

At least 19 recordsLinked to original sources

PubMed2001

Alterations of striatal dopamine receptor binding in Alzheimer disease are associated with Lewy body pathology and antemortem psychosis.

BACKGROUND: Lewy bodies (LB) are present in at least 20% to 30% of persons with Alzheimer disease (AD) and contribute to the risk of psychosis and to excess cognitive burden. OBJECTIVE: To determine whether altered striatal dopamine receptor binding is associated with LB and psychosis in AD. DESIGN: Postmortem case control. SETTING: Alzheimer's Disease Research Center at the University of Pittsburgh (Pa). PARTICIPANTS: Consecutive cases from the Alzheimer's Disease Research Center brain bank, neuroleptic free for at least 1 month prior to death, with neuropathologic diagnoses of AD with LB (AD + LB, n = 14), AD without LB (AD, n = 13), or normal brains (n = 8). MAIN OUTCOME MEASURES: Dopamine D1, D2, and D3 receptor densities, and affinities as determined by selective saturation binding studies in striatal tissue. RESULTS: Subjects with AD + LB, compared with those with AD, demonstrated increased D1 receptor density and decreased D2 and D3 receptor density. D3 receptor density was selectively increased, however, in AD subjects with a history of psychosis, independent of the presence or absence of LB. The effect of neuroleptic treatment on D3 binding was further examined in an additional group of subjects who had received neuroleptics near the time of death. Neuroleptic treatment reduced D3 affinity with no effect on D3 density. CONCLUSIONS: Alzheimer disease with LB is associated with selective alterations in dopamine receptor density, which may contribute to the distinct clinical profile of this group. The D3 receptor may be an important target of neuroleptic treatment of psychosis in AD.

Aged↗

PubMed2001

Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy study.

OBJECTIVES: To determine whether there was a different response to vitrectomy and tap/biopsy with or without systemic antibiotic treatment in the Endophthalmitis Vitrectomy Study and whether the signs and symptoms of endophthalmitis differ between diabetic and nondiabetic patients. DESIGN: A multicenter clinical trial in which patients with acute post-cataract extraction endophthalmitis were randomly assigned in a 2 x 2 factorial design to vitrectomy or tap/biopsy, in each case with or without intravenous antibiotics, and followed up for 9 months. Outcome measures included visual acuity assessed in standardized fashion. RESULTS: Fifty-eight of 420 study patients had diabetes. Diabetic patients had slightly worse vision and ocular media at the baseline assessment. Only 39% of diabetic patients compared with 55% of nondiabetic patients achieved 20/40 final vision. Both diabetic and nondiabetic patients with initial light perception (LP)-only vision had better visual results with immediate vitrectomy. For those with better than LP baseline vision, patients with diabetes achieved visual acuity of 20/40 more often with vitrectomy (57%) than with tap/biopsy (40%), but this difference was not statistically significant. Patients without diabetes did equally well with vitrectomy or tap/biopsy. CONCLUSIONS: For patients with better than LP vision, tap/biopsy is appropriate for those without diabetes. A clinical trial of a sufficient number of diabetic patients with better than LP vision is necessary to determine the best management for this group. At present, initial vitrectomy or tap/biopsy are reasonable approaches for diabetic patients with better than LP vision.

Adult↗

PubMed2001

Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: the role of child abuse.

BACKGROUND: Excitotoxicity is an important mechanism in secondary neuronal injury after traumatic brain injury (TBI). Excitatory amino acids (EAAs) are increased in cerebrospinal fluid (CSF) in adults after TBI; however, studies in pediatric head trauma are lacking. We hypothesized that CSF glutamate, aspartate, and glycine would be increased after TBI in children and that these increases would be associated with age, child abuse, poor outcome, and cerebral ischemia. METHODS: EAAs were measured in 66 CSF samples from 18 children after severe TBI. Control samples were obtained from 19 children who received lumbar punctures to rule out meningitis. RESULTS: Peak and mean CSF glycine and peak CSF glutamate levels were increased versus control values. Subgroups of patients with TBI were compared by using univariate regression analysis. Massive increases in CSF glutamate were found in children <4 years old and in child abuse victims. Increased CSF glutamate and glycine were associated with poor outcome. A trend toward an association between high glutamate concentration and ischemic blood flow was observed. CONCLUSIONS: CSF EAAs are increased in infants and children with severe TBI. Young age and child abuse were associated with extremely high CSF glutamate concentrations after TBI. A possible role for excitotoxicity after pediatric TBI is supported.

Adolescent↗

PubMed2001

Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium reabsorption in normal human volunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy.

All would agree that hypercalcemia occurs among patients with humoral hypercalcemia of malignancy (HHM) as a result of osteoclastic bone resorption. Some studies suggest that enhanced renal calcium reabsorption, which plays an important pathophysiological role in the hypercalcemia occurring in primary hyperparathyroidism, is also important pathophysiologically in HHM. Other studies have not agreed. In large part, these differences result from the inability to accurately assess creatinine and calcium clearance in critically ill subjects with HHM. To circumvent these issues, we have developed steady state 48-h PTH-related protein (PTHrP) infusion and 8-h hypercalcemic calcium clamp protocols. These techniques allow assessment of the effects of steady state PTHrP and calcium infusions in normal healthy volunteers in a setting in which renal function is stable and measurable and in which the filtered load of calcium can be matched in PTHrP- and calcium-infused subjects. Normal subjects were infused with saline (placebo), PTHrP, or calcium. Subjects receiving PTHrP, as expected, displayed mild hypercalcemia (10.2 mg/dL), suppression of endogenous PTH-(1--84), and phosphaturia. Subjects receiving the hypercalcemic calcium clamp displayed indistinguishable degrees of hypercalcemia and PTH suppression. Despite their matched degrees of hypercalcemia and PTH suppression, the two groups differed importantly with regard to fractional calcium excretion (FECa). The hypercalcemic calcium clamp group was markedly hypercalciuric (FECa averaged 6.5%), whereas FECa in the PTHrP-infused subjects was approximately 50% lower (between 2.5--3.7%), and no different from that in the normal controls, which ranged from 1.5--3.0%. These studies demonstrate that PTHrP is able to stimulate renal calcium reabsorption in healthy volunteers. These studies suggest that PTHrP-induced renal calcium reabsorption, in concert with the well established acceleration of osteoclastic bone resorption, contributes in a significant way to the hypercalcemia observed in patients with HHM.

Absorption↗

PubMed2000

Retinal detachment in the endophthalmitis vitrectomy study.

OBJECTIVES: To assess the frequency of retinal detachment following postcataract endophthalmitis and to evaluate the results of management of these detachments. METHODS: Prospective data collected as part of the Endophthalmitis Vitrectomy Study were analyzed. The study was a randomized clinical trial testing the roles of vitrectomy and intravenous antibiotics in restoring vision in patients with endophthalmitis following cataract surgery. RESULTS: The incidence of retinal detachment was 8.3% after treatment of endophthalmitis, with no difference in frequency based on whether initial management was vitrectomy or tap biopsy. The frequency of detachment was higher with more virulent organisms, poor presenting visual acuity, an open posterior capsule at presentation, and in patients who required an early additional procedure in the management of their endophthalmitis. Retinal detachment resulted in a poor visual outcome, with only 27% of patients achieving 20/40 final visual acuity compared with 55% of patients who did not develop detachment. Patients who were able to undergo surgery for their detachment had a better result, with 38% achieving 20/40 final visual acuity. Anatomic success after surgical repair of detachment was achieved in 78% of patients. CONCLUSION: Retinal detachment is a poor prognostic indicator following endophthalmitis, but surgical repair can salvage excellent vision in a substantial number of patients.

Aged↗

PubMed2000

Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in children: a preliminary report.

Adrenomedullin is a recently discovered 52-amino-acid peptide that is a potent vasodilator. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats. Adrenomedullin may represent an endogenous neuroprotectant since it is increased after focal brain ischemia. Cerebral hypoperfusion is present after traumatic brain injury (TBI) in children. We hypothesized that adrenomedullin levels would be increased in children with severe TBI. Total adrenomedullin concentrations were measured using a radioimmunometric assay. Thirty-six samples of ventricular cerebrospinal fluid (CSF) from 10 pediatric patients were collected during the first 10 days after severe TBI (GCS < 8). Control CSF was obtained from 5 children undergoing lumbar puncture, who had normal CSF parameters and no evidence of central nervous system infection. Patients underwent standard neuro-intensive care, including cerebrospinal fluid drainage. Data were analyzed using a univariate regression model. Adrenomedullin concentration was markedly elevated in CSF of children following TBI versus control (mean level 10.65 vs 1.51 fmol/ml, p = 0.006). All 36 case samples had an adrenomedullin concentration above the median value for the controls (1.52 fmol/ml). We conclude adrenomedullin is elevated in the CSF of children following severe TBI. We speculate that it participates in the endogenous response to cerebral hypoperfusion after TBI.

Adrenomedullin↗

PubMed2000

Characteristics after cataract extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study.

PURPOSE: This report describes the presenting clinical ophthalmic features and historical findings in patients with a clinical diagnosis of endophthalmitis after cataract extraction or secondary lens implant surgery screened for enrollment in the Endophthalmitis Vitrectomy Study (EVS). DESIGN: Clinic-based, cross-sectional study. PARTICIPANTS: Eight hundred fifty-four patients suspected to have endophthalmitis after cataract extraction or secondary lens implantation. METHODS: As part of the screening process for the study, an eye examination, a medical history, and demographic data were recorded in standardized form for all patients with endophthalmitis after cataract extraction or secondary lens implant surgery referred to the clinical centers, regardless of whether the patient met entry criteria. MAIN OUTCOME MEASURES: Demographics, presenting signs, and symptoms. RESULTS: The median age of individuals presenting with suspected bacterial endophthalmitis was 75 years (range, 9-100 years). Most of those screened (57.7%) were women. Seventy-nine percent of patients sought treatment within 6 weeks of surgery. Blurred vision, conjunctival injection, pain, and lid swelling were the predominant presenting symptoms in order of prevalence. Ocular pain and hypopyon, widely regarded as diagnostic of endophthalmitis, were each absent in 25% of patients. The median hypopyon height, when present, was 1.5 mm. CONCLUSIONS: The classic presentation of postoperative endophthalmitis includes reduced vision, conjunctival hyperemia, pain, hypopyon, and lid swelling within days after cataract surgery or secondary lens implantation. These were the prominent clinical findings in the EVS as well. Because pain and hypopyon, although common, were not always present, clinicians must be vigilant in postsurgical monitoring of patients.

Adolescent↗

PubMed2000

Psychotic symptoms in Alzheimer's disease are not associated with more severe neuropathologic features.

Psychotic symptoms in Alzheimer's disease (AD) have been associated with increased rates of cognitive impairment and functional decline. Prior studies have been conflicting with regard to whether AD patients with psychosis (AD+P) have evidence of more severe neuropathologic findings at postmortem exam. We examined the severity of neuritic plaques and neurofibrillary tangles in six brain regions--middle frontal cortex, hippocampus, inferior parietal cortex, superior temporal cortex, occipital cortex, and transentorhinal cortex-in 24 AD+P subjects and 25 matched AD subjects without psychosis (AD-P). All analyses controlled for the presence of cortical Lewy bodies, and corrected for multiple comparisons. We found no significant associations between neuritic plaque and neurofibrillary tangle severity and AD+P, and no significant associations with any individual psychotic symptom. The association of AD+P with a more rapidly progressive course of AD appears to be mediated by a neuropathologic process other than increased severity of plaque and tangle formation.

Aged↗

PubMed2000

Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children after severe traumatic brain injury.

OBJECTIVES: To determine whether bcl-2, a protein that inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in infants and children after traumatic brain injury (TBI) and to examine the association of bcl-2 concentration with clinical variables. STUDY DESIGN: Bcl-2 was measured in CSF from 23 children (aged 2 months-16 years) with severe TBI and from 19 children without TBI or meningitis (control subjects) by enzyme-linked immunosorbent assay. CSF oligonucleosome concentration was also determined as a marker of DNA degradation. Brain samples from 2 patients undergoing emergent decompressive craniectomies were analyzed for bcl-2 with Western blot and for DNA fragmentation with TUNEL (terminal deoxynucleotidyl-transferase mediated biotin-dUTP nick-end labeling). RESULTS: CSF bcl-2 concentrations were increased in patients with TBI versus control subjects (P =.01). Bcl-2 was increased in patients with TBI who survived versus those who died (P =.02). CSF oligonucleosome concentration tended to be increased after TBI (P =.07) and was not associated with bcl-2. Brain tissue samples showed an increase in bcl-2 in patients with TBI versus adult brain bank control samples and evidence of DNA fragmentation within cells with apoptotic morphology. CONCLUSIONS: Bcl-2 may participate in the regulation of cell death after TBI in infants and children. The increase in bcl-2 seen in patients who survived is consistent with a protective role for this anti-apoptotic protein after TBI.

Adolescent↗

PubMed2000

Isoflurane improves long-term neurologic outcome versus fentanyl after traumatic brain injury in rats.

Despite routine use of fentanyl in patients after traumatic brain injury (TBI), it is unclear if it is the optimal sedative/analgesic agent. Isoflurane is commonly used in experimental TBI. We hypothesized that isoflurane would be neuroprotective versus fentanyl after TBI. Rats underwent controlled cortical impact (CCI) and received 4 h of N2O/O2 (2:1) and either fentanyl (10 microg/kg i.v. bolus, 50 microg/kg/h infusion) or isoflurane (1% by inhalation) with controlled ventilation. Shams underwent identical preparation, without CCI. Functional outcome (beam balance, beam walking, Morris water maze [MWM] tasks) was assessed over 20 days. Lesion volume and hippocampal neuron survival were quantified on day 21. Additional rats underwent identical CCI and anesthesia with intracranial pressure (ICP) monitoring, and brain water content was assessed. Motor and MWM performances were better in injured rats treated with isoflurane versus fentanyl (p < 0.05). CA1 hippocampal damage was attenuated in isoflurane-treated rats (p < 0.05). Fentanyl-treated rats had higher mean arterial blood pressure after injury (p < 0.05); however, ICP and brain water were similar between groups. Isoflurane improved functional outcome and attenuated damage to CA1 versus fentanyl in rats subjected to CCI. Isoflurane may be neuroprotective by augmenting cerebral blood flow and/or reducing excitotoxicity, not by reducing ICP or brain water content. Alternatively, fentanyl may be detrimental. Isoflurane may mask beneficial effects of novel agents tested in TBI models. Additionally, fentanyl may not be optimal early after TBI in humans.

Analgesics, Opioid↗

PubMed2000

Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury.

OBJECTIVE: To determine interleukin (IL)-8 concentrations in ventricular cerebrospinal fluid from children with severe traumatic brain injury (TBI). DESIGN: Prospective study. SETTING: University children's hospital. PATIENTS: Twenty-seven children hospitalized with severe TBI (Glasgow Coma Scale score < or =8), seven children with cerebrospinal fluid culture-positive bacterial meningitis, and twenty-four age-equivalent controls. INTERVENTIONS: Placement of an intraventricular catheter and continuous drainage of cerebrospinal fluid. MEASUREMENTS AND MAIN RESULTS: Median [range] cerebrospinal fluid IL-8 concentration in children with TBI (0-12 hrs) (4,452.5 [0-20,000] pg/mL) was markedly greater than that in controls (14.5 [0-250]) (p < .0001) and equivalent to concentrations in children with meningitis (5,300 [1,510-22,000] pg/mL) (p = .33). Cerebrospinal fluid IL-8 remained increased in children with severe TBI for up to 108 hrs after injury. Univariate logistic regression analysis demonstrated an association between cerebrospinal fluid IL-8 and child abuse (p = .07) and mortality (p = .01). Multivariate analysis demonstrated a strong, independent association between cerebrospinal fluid IL-8 and mortality (p = .01). CONCLUSIONS: The data are consistent with an acute inflammatory component of TBI in children and suggest an association between cerebrospinal fluid IL-8 and outcome after TBI. IL-8 may represent a potential target for anti-inflammatory therapy.

Acute Disease↗

PubMed2000

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are increased in the plasma of children with sepsis-induced multiple organ failure.

OBJECTIVES: To determine concentrations of circulating adhesion molecules endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in children with sepsis-induced multiple organ failure (MOF), and to determine associations among increased concentrations of these circulating adhesion molecules and important outcome measures. DESIGN: Prospective study. SETTING: University pediatric intensive care unit. PATIENTS: A total of 77 consecutive children with sepsis and 14 acutely ill children without sepsis. INTERVENTIONS: Plasma E-selectin, ICAM-1, and VCAM-1 concentrations and organ failure index (indicating number of failed organ systems) were determined in 77 children on days 1 and 3 of sepsis, and in 14 control children on pediatric intensive care unit day 1. Multivariate logistic regression analysis was used to determine associations between adhesion molecule concentrations and clinically relevant outcome measures. MEASUREMENTS AND RESULTS: Plasma concentrations of E-selectin, ICAM-1, and VCAM-1 were increased in children with sepsis vs. control on day 1 (p < .05). Plasma VCAM-1 (but not ICAM-1 or E-selectin) was increased in children with more than three organ failures vs. children with less than three organ failures (p < .05). Plasma ICAM-1 and VCAM-1 (but not E-selectin) concentrations independently predicted number of organs failed and development of more than three organ failures. Plasma ICAM-1 and VCAM-1 also predicted mortality and development of sequential (pulmonary/hepatic/renal) MOF (p < .05). CONCLUSIONS: The pronounced and persistent increase in plasma VCAM-1 and ICAM-1 that occurs in children with sepsis and persistent MOF may indicate a phenotypic change in endothelium toward a more proinflammatory state. Alternatively, the source for these adhesion molecules may be activated leukocytes and other cell types. Future studies are required to determine the role of ICAM-1 and VCAM-1 in the pathogenesis of sepsis-induced MOF.

Adolescent↗

PubMed2000

No long-term benefit from hypothermia after severe traumatic brain injury with secondary insult in rats.

OBJECTIVES: To evaluate the effect of application of transient, moderate hypothermia on outcome after experimental traumatic brain injury (TBI) with a secondary hypoxemic insult. DESIGN: Prospective, randomized study. SETTING: University-based animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: All rats were subjected to severe TBI followed by 30 mins of moderate hypoxemia, associated with mild hypotension. Rats were randomized to three groups: a) normothermia (37 degrees C + 0.5 degrees C); b) immediate hypothermia (32 degrees C +/- 0.5 degrees C initiated after trauma, before hypoxemia); and c) delayed hypothermia (32 degrees C +/- 0.5 degrees C after hypoxemia). The brain temperature was controlled for 4 hrs after TBI and hypoxemia. MEASUREMENTS AND MAIN RESULTS: Animals were evaluated after TBI for motor and cognitive performance using beam balance (days 1-5 after TBI), beam walking (days 1-5 after TBI), and Morris Water Maze (days 14-18 after TBI) assessments. On day 21 after TBI, rats were perfused with paraformaldehyde and brains were histologically evaluated for lesion volume and hippocampal neuron counts. All three groups showed marked deficits in beam balance, beam walking, and Morris Water Maze performance. However, these deficits did not differ between groups. There was no difference in lesion volume between groups. All animals had significant hippocampal neuronal loss on the side ipsilateral to injury, but this loss was similar between groups. CONCLUSIONS: In this rat model of severe TBI with secondary insult, moderate hypothermia for 4 hrs posttrauma failed to improve motor function, cognitive function, lesion volume or hippocampal neuronal survival. Combination therapies may be necessary in this difficult setting.

Animals↗

PubMed2000

Effect of neutropenia and granulocyte colony stimulating factor-induced neutrophilia on blood-brain barrier permeability and brain edema after traumatic brain injury in rats.

OBJECTIVE: Granulocyte colony stimulating factor (GCSF) has been used to increase systemic absolute neutrophil count (ANC) in patients with severe traumatic brain injury to reduce nosocomial infection risk. However, the effect of increasing systemic ANC on the pathogenesis of experimental traumatic brain injury has not been studied. Thus, we evaluated the effect of systemic ANC on blood-brain barrier (BBB) damage and brain edema after traumatic brain injury in rats. DESIGN: Experimental study. SETTING: Research laboratory at the University of Pittsburgh, PA. SUBJECTS: Forty-three adult male Sprague-Dawley rats. INTERVENTIONS: Protocol I: rats were randomized to receive either vinblastine sulfate to reduce ANC, GCSF to increase ANC, or saline before controlled cortical impact (CCI) of moderate overall severity. Evans blue was used to assess BBB damage at 4-24 hrs after CCI. Protocol II: rats received GCSF or saline before CCI. Brain edema was estimated at 24 hrs using wet - dry) / wet weight method. Protocol III: rats received GCSF or saline before CCI. Brain neutrophil accumulation was estimated at 24 hrs using a myeloperoxidase assay. MEASUREMENTS AND MAIN RESULTS: Physiologic variables were controlled before CCI was maintained at normal in all animals before traumatic brain injury. No rats were anemic, hypoglycemic, or hypotensive before CCI. Protocol I: compared with control, systemic ANC decreased in vinblastine-treated rats and increased in GCSF-treated rats. BBB damage correlated with systemic ANC. Protocol II: mean systemic ANC before traumatic brain injury increased 15-fold in rats given GCSF vs. control; however no difference in brain edema was observed at 24 hrs after injury between groups. Protocol III: median systemic ANC at the time of CCI was increased ten-fold in rats given GCSF vs. control. No difference in brain myeloperoxidase activity 24 hrs after CCI was observed in rats treated with GCSF vs. control. CONCLUSIONS: Systemic ANC influences BBB damage after traumatic brain injury produced by CCI. Because BBB damage and brain edema are discordant, mechanisms other than BBB damage likely predominate in the pathogenesis of brain edema after contusion. The implications of increased BBB permeability with the administration of GCSF in our model remains to be determined. Increasing systemic ANC before CCI with GCSF administration does not increase posttraumatic brain neutrophil accumulation or brain edema after CCI in rats. The finding that neutrophil infiltration is not enhanced by systemic neutrophilia suggests that the ability of GCSF-stimulated neutrophils to migrate into injured tissue may be impaired. Further studies are needed to evaluate the effects of GCSF administration on secondary injury and functional outcome in experimental models of traumatic brain injury.

Animals↗

PubMed1999

Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease.

OBJECTIVE: To examine whether the use of psychiatric medication and the presence of abnormal behaviors affects the progression of Alzheimer disease. DESIGN: Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: (1) Mini-Mental State Examination score of 9 or lower; (2) Blessed Dementia Rating Scale score of 15 or higher for activities of daily living; (3) nursing home admission; and (4) death, evaluated using a proportional hazard model with 9 variables: psychosis, insomnia, wandering, aggression, psychomotor agitation, depression, and use of antidepressants, antipsychotic agents, or sedatives/hypnotics. SETTING: Multidisciplinary dementia research clinic. PATIENTS: We examined baseline and follow-up behavioral symptoms and the use of psychiatric medication in 179 mildly to moderately impaired patients with probable Alzheimer disease participating in a longitudinal study of dementia. Patients were observed from 2.4 to 172 months (mean duration +/- SD, 49.5+/-27.4 months). RESULTS: Nine patients (5%) were taking sedatives/ hypnotics; 16 (9%), antipsychotic agents; and 22 (12%), antidepressants at study entry. Patients taking antipsychotic agents had lower Mini-Mental State Examination scores and higher Blessed Dementia Rating Scale scores for activities of daily living than patients not taking any medication. Using proportional hazard analysis with time-dependent covariates for individual psychiatric symptoms and medications, we found that the development of psychosis was associated with functional decline (time to Blessed Dementia Rating Scale score of > or =15), institutionalization, aggression, and agitation with functional decline after adjusting for age at study entry, education, Mini-Mental State Examination scores, and Blessed Dementia Rating Scale scores. Use of antipsychotic medication was associated with functional decline, and sedatives/hypnotics with death. Neither the presence of psychiatric symptoms nor use of medication was associated with rate of cognitive decline (time to Mini-Mental State Examination score of < or =9). CONCLUSIONS: These findings indicate that the use of antipsychotic agents and sedatives can affect the natural course of Alzheimer disease. Psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account.

Aged↗

PubMed1999

Selecting, developing, and evaluating research instruments.

The goal of this paper is to provide researchers who are not experts in psychometric theory with a concise guide to instrument selection, development and evaluation. Issues of context - factors related to the setting or population in which an instrument will be used - and psychometrics - the functioning of an instrument within a given context - are reviewed and discussed. Finally, four categories or types of instruments, and the psychometric analyses that are necessary for establishing the reliability and validity of each type, are described.

Humans↗

PubMed1999

Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury.

OBJECTIVE: To measure quinolinic acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF quinolinic acid concentrations to clinically important variables. DESIGN: A prospective, observational study. SETTING: The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university-based children's hospital. PATIENTS: Seventeen critically ill children following severe TBI (Glasgow Coma Scale score <8) whose care required the placement of an intraventricular catheter for continuous drainage of CSF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 mos to 16 yrs (mean 6.0 yrs). CSF was collected immediately on placement of the ventricular catheter and daily thereafter. Quinolinic acid concentration was measured by gas chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per patient). CSF quinolinic acid concentration progressively increased after injury (p = .034, multivariate analysis) and was increased in nonsurvivors vs. survivors (p = .002, multivariate analysis). CSF quinolinic acid concentration was not associated with age. Although overall CSF quinolinic acid concentration was not associated with shaken injury (p = .16, multivariate analysis), infants suffering with shaken infant syndrome had increased admission CSF quinolinic acid concentrations compared with children with accidental mechanisms of injury (p = .027, Mann-Whitney Rank Sum test). CONCLUSIONS: A large and progressive increase in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI in children. The increase is strongly associated with increased mortality. Increased CSF quinolinic acid concentration on admission in children with shaken infant syndrome could reflect a delay in presentation to medical attention or age-related differences in quinolinic acid production. These findings raise the possibility that quinolinic acid may play a role in secondary injury after TBI in children and suggest an interaction between inflammatory and excitotoxic mechanisms of injury following TBI.

Accidents, Traffic↗

PubMed1999

Microbiologic yields and complication rates of vitreous needle aspiration versus mechanized vitreous biopsy in the Endophthalmitis Vitrectomy Study.

PURPOSE: To compare the microbiologic yields and complication rates associated with vitreous needle tap and vitreous biopsy in the Endophthalmitis Vitrectomy Study (EVS). METHODS: Of 420 EVS patients with postoperative endophthalmitis, 201 received immediate vitreous tap or biopsy (without pars plana vitrectomy) by random assignment and 193 completed 9-12 months of follow-up. Vitreous specimens were obtained by biopsy with a 20-gauge vitrectomy cutting instrument or by needle tap with a 22-27-gauge needle. If resistance to aspiration by needle tap was noted, a vitreous biopsy was performed. RESULTS: Of 201 patients undergoing tap or biopsy, 70 (35%) had needle tap, 127 (63%) had mechanized biopsy, and 4 (2%) had initial needle tap that was aborted to mechanized biopsy ("abort" eyes). Intraoperative hyphema occurred in 2 tap eyes (3%), 3 biopsy eyes (2%), and 0 (0%) abort eyes. Postoperative retinal detachment developed in 8 (11%) tap eyes, 10 (8%) biopsy eyes, and 0 (0%) abort eyes (not significant). Respective rates of culture and gram stain positivity were 69% and 42% in tap eyes and 66% and 41% in biopsy eyes (not significant). The rate of severe visual loss (final acuity <5/200) was significantly higher in tap eyes (16 eyes, 24%) compared with biopsy eyes (13 eyes, 11%) and abort eyes (0 eyes, 0%; P = 0.043). The difference was largely explained by the greater proportion of virulent organisms in the tap eyes compared with biopsy eyes. When visual acuity outcome was defined by other thresholds (20/40 and 20/100), the difference was not significant. CONCLUSIONS: This study showed no significant differences between mechanized vitreous biopsy and needle tap with respect to microbiologic yield, operative complications, short-term (9-12 months) retinal detachment risk, or visual outcome. Choice of vitreous sampling procedure must depend on the clinical judgment of the surgeon.

Biopsy, Needle↗